deamino-arginine-vasopressin and Wolfram-Syndrome

Initiation of desmopressin acetate (DDAVP) for untreated diabetes insipidus (DI) in Wolfram syndrome (WS) causes abrupt volume expansion resulting in particularly high secretion of Atrial Natriuretic Peptide (ANP) and/or Brain Natriuretic Peptide (BNP), which in turn blocks all stimulators of zona glomerulosa steroidogenesis, resulting in secondary mineralocorticoid deficiency and acute hyponatremia, causing renal salt wasting (RSW). Two sisters, a 19-y-old girl (A) and a 7-y-old girl (B) with WS, presented with severe polyuria-polydipsia due to never treated DI. Both had neurogenic bladder and "B" had severe hydronephrosis secondary to untreated grade III bilateral vesicoureteral reflux. They initiated therapy with oral melt DDAVP which resulted in RSW. ANP was found ×50 and BNP ×2-4 fold elevated. Fludrocortisone 100-200 × 2 μg/d controlled natriuresis and restored electrolytes to normal within 48 h. Fludrocortisone treatment rescues otherwise potentially life-threatening hyponatremia due to RSW and the secondary mineralocorticoid deficiency driven by elevated ANP and/or BNP, caused by sudden volume expansion following DDAVP initiation.

Topics: Atrial Natriuretic Factor; Child; Deamino Arginine Vasopressin; Female; Fludrocortisone; Humans; Hyponatremia; Wolfram Syndrome; Young Adult

Topics: Antidiuretic Agents; Child; Chromosomes, Human, Pair 4; Deamino Arginine Vasopressin; Diabetes Insipidus; Family Health; Female; Hearing Loss, Sensorineural; Homozygote; Humans; Hydronephrosis; Membrane Proteins; Mothers; Mutation; Treatment Outcome; Uniparental Disomy; Urinary Bladder, Neurogenic; Wolfram Syndrome

The 6-year follow-up of a patient affected by Wolfram's syndrome, a rare disease characterized by diabetes insipidus (DI), diabetes mellitus (DM), optic atrophy (OA), neurosensory deafness (D), atony of the urinary tract and other abnormalities (DIDMOAD or Wolfram's syndrome), is described. Our patient has diabetes insipidus, diabetes mellitus, abnormal audiograms, without subjective evidence of hearing loss, and dilatation of the urinary tract. Diagnosis was suspected at the age of 8 years. Diabetes mellitus was the first manifestation and treatment with insulin was necessary. Desmopressin therapy decreased dramatically the daily urinary output. In view of the significant morbidity and mortality from renal failure associated with recurrent urinary infections, we have drawn special attention to the urological manifestations of the syndrome. During the follow-up, the patients underwent some investigations, such as renal ultrasound and echotomography and cystourethroscopy. Outstanding results of these studies are severe bilateral hydronephrosis with dilatated ureters and loss of renal tissue. The particular finding is the presence of posterior urethral valves with obstructed bladder. The anatomical outlet obstruction are variable and may be disastrous. There may be failure to thrive, sepsis, anemia be disanal failure. In such instances corrective surgery could improve bladder and ureteral functions.

Topics: Adolescent; Child; Child, Preschool; Deamino Arginine Vasopressin; Diabetes Complications; Diabetes Insipidus; Diabetes Mellitus; Drinking; Follow-Up Studies; Humans; Insulin; Male; Polyuria; Urography; Urologic Diseases; Wolfram Syndrome